Targeting the IDH2 Pathway in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase ( IDH ) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation. Targeting IDH2 is compelling, as it is an early and stable mutation in AML. Enasidenib, a specific small-molecule inhibitor of IDH2, recently gained FDA approval for the treatment of patients with relapsed/refractory IDH2 -mutated AML. In this review, we will focus on the indications and efficacy of enasidenib in the treatment of patients with IDH2 -mutated AML. Clin Cancer Res; 1-6. ©2018 AACR.